Objective To evaluate the effects of mild hypothermia performed at different times on the levels of glutamate, Bcl-2 and Bax during global cerebral ischemia-reperfsusion (I/R) in rats. Methods Twenty-four male SD rats weighing 230-270 g were randomly divided into 4 groups according to the time at which mild hypothermia was performed ( n =6 each): group A, B, C and D. Global cerebral ischemia was produced by occlusion of 4 vessels (cauterization of bilateral vertebral arteries and occlusion of bilateral common carotid arteries) in the 4 groups. In group B, C and D, the nasopharyngeal temperature was reduced to 32.5-33.5 ℃ and maintained for 1 h. Ischemia was performed after termination of cooling in group B. While ischemia was performed, cooling was started in group C. While reperfusion was performed, cooling was started in group D. Rewarming was started after termination of cooling in group B, C and D. Samples of dialysate in hippocampal CA1 area were collected every 10 min during 100 min reperfusion for determination of glutamate concentrations by high-performance capillary electrophoresis with laser-induced fluorescence detection ( HPCE-LIF). The brain tissues were taken at 3 h of reperfusion for determination of the expression of Bax and Bcl-2 in hippocampal CA1 area, and the ratio of Bcl-2/Bax was calculated. Results Compared with group A, the glutamate concentrations were significantly decreased, the Bcl-2 expression was up-regulated, the Bax expression was down-regulated and the ratio of Bcl-2/Bax was increased in the other thee groups ( P ＜ 0.05). Compared with group B, the Bcl-2 expression was significantly down-regulated, the Bax expression was up-regulated and the ratio of Bcl-2/Bax was decreased in group C ( P ＜0.05). The glutamate concentrations were significantly increased, the Bax expression was up-regulated and the ratio of Bcl-2/Bax was decreased in group D compared with group C ( P ＜ 0.05 ). Conclusion The earlier cooling is performed, the better the cerebral protective effect is during global cerebral I/R in rats.

Objective To evaluate the clinical outcome of severe ulcerative colitis(UC)and to find the factors related to treatment and outcome.Methods Forty one hospitalized patients with UC during 1988-2004 were retrospectively reviewed.Data were recorded including the onset,symptoms,signs, laboratory,endoscopic,radiologic and pathologic findings,as well as the processes of clinical treatment. The patients who undergone surgery were also analysed.Results Forty one of 144(28.5%)hospital ized patients were suffered from severe UC,and among them 92.7%(38/41)had pancolitis.The patients who had first onset,chronic persistent,chronic recurrent type were account for 36.9%(15/41),36.9%(15/41) and 26.8%(11/41),respectively.The steroids treatment played the main role in the inducing remission of severe UC(61.0%).Thirty one cases(75.6%)could be relieved by drug therapy.Seven cases(17.1%) were progressed to have operation.The age of early onset,pancolitis,low hemoglobin and serum albumin levels and need of intravenous steroids treatment were associated with the need of surgery.Conclusions Most of the severe UC patients respond well to the medical therapy,but for some non-responding or steroids depending individuals,after a reasonable duration of treatment,surgery should be considered.

A review of the system background for the multi-institution physician practice in China,and an analysis for the specific constraints for physicians of public hospitals to embrace such a practice On this basis, the paper probed into the measures to encourage the physicians for doing so. The measures recommended include advanced design, improvement of the quality of care and safety mechanism,incentives mechanism, mandatory enforcement of medical liability insurance to minimize risk exposure of such a practice, aiming at advancement of this practice.

Objective To evaluate the effects of supine and prone position on ventilation function in neonates in the initial six-hour period after weaning. Methods Sixty-four neonates weaned from mechanical ventilation and with normal body temperature hospitalized from Sep. 2004 to Apr. 2006 in our NICU were randomly divided into prone group and supine group. All of them were oxygen administrated through head net, oxygen flow rate was adjusted continously to keep SpO2 at normal level by monitoring SpO2 and RR. FiO2、RR were recorded at 15 minutes,1 h,2 h,3 h,4 h,5 h,6 h after weaning. Arterial blood gas was meas-ured at 1 h ,6 h after weaning and A-aDO2, RI, OI were calculated. Results (1) At 1～6 h after weaning the values of FiO2 in prone group were significantly lower than those in the supine group(P<0.01). (2) After weaning there was a decreasing tendency of RR in the prone group and the significant decrease was found at 4 h ,5 h ,6 h compared with supine group (P<0.01). (3) At 1h and 6h after weaning, the value of PaO2 and OI were significantly higher and the value of A-aDO2, RI were lower in the prone group than in the supine group(P<0.05,P<0.01). (4) At 6 h the PaCO2 in prone group were obviously higher than that in supine group (P<0.05). Conclusion At first 6h after weaning prone position can improve ventilation functions.

Objective To detect ret mutations in two Chinese families with multiple endocrine neoplasia type 2A(MEN2A).Methods In our study,9 members from these two families including 3 patients were recruited.Polymerase chain reaction(PCR)and direct gene sequencing of PCR products by an automated DNA sequencer were applied to scan the entire 21 exons of ret proto-oncogene in the leukocyte DNA of the subjects.Results Two missense mutations were detected in exon11 of the ret proto-oncogene.One was C634R in the 2 patients from a family and the other was C634Y in 2 subjects from another family(one was the patient).Two heterozygous variants(A45A and L769L)in these 4 subjects were revealed.Conclusion Two mutations(C634R and C634Y)are detected in two families with MEN2A.Direct DNA sequencing analysis can diagnose MEN2A at gene level,which is helpful in making clinical management of the disease and in diagnosing earlier in their offspring.

Humans ; Platelet-Derived Growth Factor ; Pulmonary Fibrosis

Objective: To investigate the effects of processing and compatibility of ginger for the treatment of cold asthma rats at the metabolomics level by gas chromatography-mass spectrometry (GC-MS). Methods: The rats of cold asthma were established by ovalbumin (OVA) + ice water bath. The rats divided randomly into the control group, model group, Linggan Wuwei (fresh/dry/stir- frying) Jiangxin Decoction group and the positive drug Guilong Kechuanning group. The pathological changes of lung tissue were observed by HE staining; The inflammatory cell count in BALF and the content of IgE, IL-4 and IFN-γ in serum were determined. GC-MS was used to conduct the non-targeted metabolomics study to search the serum and urine related differential metabolites in rats with cold asthma, and MetaboAnalyst was used to construct related metabolic pathways. Results: The results showed that Linggan Wuwei (fresh/dry/stir-frying) Jiangxin Decoction improved the pathological changes of rat lung tissue, significantly reduced the BALF inflammatory cell count in BALF and IgE and IL-4 levels in serum, and increased IFN-γ levels. Compared with the control group, 37 differential metabolites (15 in serum and 22 in urine) were screened in cold asthma rats. And seven metabolic pathways involving energy metabolism, oxidative stress may be associated with cold asthma by Metaboanalysis pathway analysis. The overall metabolic profile of the cold asthma rats with the intervention of Linggan Wuwei (fresh/dry/stir-frying) Jiangxin Decoction tended to normal levels. The effect of Linggan Wuwei (dry) Jiangxin Decoction on cold asthma was better than Linggan Wuwei (fresh/stir-frying) Jiangxin Decoction. Conclusion: It is more reasonable to process ginger into dried ginger in Linggan Wuwei Jiangxin Decoction against cold asthma. Ginger processing-compatibility may play a therapeutic role in cold asthma rats by regulating energy metabolism and oxidative stress.

OBJECTIVE: To compare the setting methods for biologics data protection period between America and Japan, in order to provide suggestions for China. METHODS: We made a contrastive study of American "break even" model and Japanese "risk management evaluation" model by using method introduction and characteristic analysis. RESULTS: The two setting methods in the US and Japan focus on different system objectives, respectively. The Chinese choice of setting method needs to combine the feasibility of setting methods and the national conditions and policy goals for comprehensive consideration. CONCLUSION: At present and the future for a long time, China's pharmaceutical industry is still in the "imitation to innovation" stage, and drug safety issues remain the core task. Therefore, the period of biologics data protection should be rationally set up by using "risk management evaluation" model as the base, "break even" model as supplement, so as to bring the three policy effects such as innovation incentive, the improvement of innovative drugs availability and strengthening the drug post-market safety monitoring.

OBJECTIVE: To make a comparative analysis on the expedited approach for new drug review in the USA, the European Union, and Japan, and to provide references for China. METHODS: Through analyzing the mechanism and implementation performance of each expedited approach, and summarizing its characteristics, this paper puts forward some suggestions according to the situation of the reform for new drug review in China. RESULTS: Compared with the US, EU and Japan, our country is gradually laying emphasis on the value of clinical curative effect when to apply expedited approach, but there is still a large gap on system setting. CONCLUSION: Hence this paper suggests to draw lessons from foreign "multi-channel, full coverage" concept, and gradually to establish a new multi-channel system of expedited review approach on the basis of perfecting our country's priority review approach, thereby accelerating the process of new drugs which have high clinical value.

Objective To compare the effectiveness and safety of raltitrexed and fluorouracil(FU)/leucovorin (LV) combined with oxaliplatin for advanced colorectal cancer. Methods Fifty patients with advanced colorectal cancer diagnosed by histopathology or cytology were randomly divided into two groups with 25 cases each by envelope, but 1 case lost. Patients in experimental group were treated with raltitrexed (3 mg/m2, ≥ 15 min intravenously) combined with oxaliplatin (130 mg/m2 on day 1 ), patients in control group were treated with FU/LV combined with oxaliplatin:LV 100 mg/m2 infusion (over 2 h, from day 1 to day 3 ) followed by FU (400 mg/m2 infusion in 2 h and 600 mg/m2 continuous infusion from day 1 to day 3 ),combined with oxaliplatin ( 130 mg/m2 on day 1 ), 3 weeks were as one cycle. Patients received 6 or less cycles until disease progressed or toxicity could not be tolerated. Results Effective rate was 37.50%(9/24)and 33.33%(8/24) in experimental group and control group respectively (P＞ 0.05). Disease control rate in experimental group was 83.33% (20/24) while in control group was 70.83% ( 17/24 ) (P ＞ 0.05 ). The median time of progression-free survival (PFS) in experimental group and control group was 11.0 months and 9.0 months respectively (95%CI 8.643-11.357,P =0.015). Main adverse effects were anorexia, vomiting, neutropenia, thrombopenia, anemia, neurotoxicity, fatigue, aminotransferase abnormality, and so on. There was no statistic difference between two groups in side effects(P ＞ 0.05). Conclusions Raltitrexed combined with oxaliplatin is an effective regimen for the advanced colorectal cancer. Compared with traditional FU-based regimen, it is more convenient. Patients will have less venous exposure time and hospital days.Effective rate and mean survival time are superior or not inferior in raltitrexed treatment to that of FU-based regimen. Raltitrexed combined with oxaliplatin is worthy to be recommended in treating colorectal cancer.